Alcohol metabolism increases the replication of hepatitis C virus and attenuates the antiviral action of interferon.
The interactions between hepatitis C virus (HCV) and alcohol metabolism are not well understood. To determine the effect that alcohol metabolism has on HCV replication and the antiviral action of interferon (IFN), Huh-7 cells that harbor HCV replication and metabolize ethanol via the introduced expression of cytochrome P450 2E1 (Cyp2e1) were treated with ethanol and IFN-alpha. Treatment of these cells with ethanol (0-100 mmol/L) significantly increased HCV replication. This effect was dependent on Cyp2e1 expression and alcohol-metabolized oxidative stress (OS), because the antioxidant N-acetylcysteine blocked this effect. Furthermore, the anti-HCV action of IFN-alpha was attenuated in the presence of ethanol metabolism, most likely via attenuation of Stat1 tyrosine-701 phosphorylation. These in vitro results mimic what is often noted clinically, and further dissection of this model system will aid in our understanding of interactions between HCV and alcohol metabolism.
McCartney
Erin M
EM
Infectious Diseases Laboratories, Institute of Medical and Veterinary Science, University of Adelaide, Adelaide, South Australia, Australia.
Semendric
Ljiljana
L
Helbig
Karla J
KJ
Hinze
Susan
S
Jones
Brett
B
Weinman
Steven A
SA
Beard
Michael R
MR
D002460:Cell Line; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects*
D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1